Rash/Lesion Start Up From Methylation Protocols

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I have been posting intermittently on the B12-The Hidden Story thread but the thread is so long now and doesn't seem to get much traffic. I am a newer member and very thankful to have found this forum. I didn't know whether starting a new thread would be a good idea, but here goes.

On that thread I have been able to discern, that some develop a rash/hive like reaction when starting methylation protocols, ie; Freddds or Rich VanK. I seem to be one of those rare occurences. I noted this on that particular thread to no address of this particular issue. This rash/hive reaction was preceeded by intense itching. This is an itching I recognize from past analphylactic reactions to medications. I came across a post on another thread in which then lead me to mastocytosis and the similarities are nagging me.

I have now come across some information in which has lead me to investigate Histamine in relation to Methylation. This is my understanding so far. I am looking for some input please.

So in terms of methylation, if a block is in existence, then histamine levels rise because histamine is deactivated by SAMe. And in terms of methylation, if a block exists, then a methyl group from methionine cannot take place with SAMe, so histamine cannot be deactivated. It is my understanding that Vitamin B12 and folates are known to cause the release of histamine. So when starting this protocol, I experienced this rash/hives because my body released histamine, and due to a block in my methylation somewhere, was unable to deactivate it because there was no methyl donor to SAMe?

So why is this occurence and me so rare? What is this supposed to indicate to me? If mastocytosis was a consideration here then what new considerations should I have while doing the methylation protocols? Freddd? Rich VanK? Someone? Should I be supplementing SAMe to help improve this situation until my methylation catches up?

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I have had 3 severe anaphylactic reactions in my medical history and one doctor afraid to administer any pain reliever besides aspirin. It didn't really mean anything to me at the time, because I have never been in need of pain management other than the multiple sugeries connected with my middle ear.

Those 3 reactions were to coedine, hydrocodone, and Inderal. Coedine and hydrocodone resulted in whole body erythema and circulatory collapse in which I was hopsitialized. Inderal, I was already admitted, and given this prior to surgery for a migraine. I went down in the pre-surgical unit with massive mast cell degranulation, severe itching, and loss of consciousness. Never seen a presurgical unit move so fast or a physician show up so fast. Those reactions took months to recover from.

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hi LaurieL, although most people consider B12 to be safe and have no side effects, it can have side effects in some people, once of these is itching and hives here's a link about it http://ezinearticles.com/?The-Side-Effects-Of-Vitamin-B12&id=816035 so that might be what your experiancing. Not really an expert on methylation protocols, but they seem to involve taking alot of different suppliments most of which can have side effects in some people, and when they're all taken at once there is a chance of interactions between the different suppliments. hope this helps all the best

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I have had 3 severe anaphylactic reactions in my medical history and one doctor afraid to administer any pain reliever besides aspirin. It didn't really mean anything to me at the time, because I have never been in need of pain management other than the multiple sugeries connected with my middle ear.

Those 3 reactions were to coedine, hydrocodone, and Inderal. Coedine and hydrocodone resulted in whole body erythema and circulatory collapse in which I was hopsitialized. Inderal, I was already admitted, and given this prior to surgery for a migraine. I went down in the pre-surgical unit with massive mast cell degranulation, severe itching, and loss of consciousness. Never seen a presurgical unit move so fast or a physician show up so fast. Those reactions took months to recover from.

I'm sorry to hear about your problems with histamine and anaphylactic reactions. I would like to help you, but I am a researcher, not a licensed physician, and cannot give medical advice. As you have described, anaphylactic reactions are quite serious, and I do not feel qualified or authorized to give advice about them.

I suggest that you work with a physician, and ask the physician about substances that can lower histamine production, such as quercetin, or antihistamines that can block histamine receptors. I would also suggest that you ask your physican to test you for copper deficiency.

It's true that one of the main pathways for breaking down histamine involves methyation. However, that's the intracellular reaction. The extracellular one uses an enzyme called diamine oxidase. The skin-type reactions result from a deficiency in the activity of this enzyme. It requires copper as a cofactor, and some people have inherited polymorphisms in it, which can lower its activity.

Department of Dermatology, University of Bonn, Bonn, Germany.
Abstract

Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism.

Genetic polymorphisms for histamine-metabolizing enzymes are responsible for interindividual variation in histamine metabolism and are associated with diverse diseases. Initial reports on polymorphisms of histamine-related genes including those coding for the enzymes histidine decarboxylase (HDC), diamine oxidase (ABP1) and histamine N-methyltransferase (HNMT), as well as histamine receptor genes, often have pointed to polymorphisms that occur with extremely low frequencies or that could not be verified by later studies. In contrast, common and functionally significant polymorphisms recently described have been omitted in many association studies. In this review we analyze allele frequencies, functional and clinical impact and interethnic variability on histamine-related polymorphisms. The most relevant nonsynonymous polymorphisms for the HDC gene are rs17740607 Met31Thr, rs16963486 Leu553Phe and rs2073440 Asp644Glu. For ABP1 the most relevant polymorphisms are rs10156191 Thr16Met, rs1049742 Ser332Phe, and particularly because of its functional effect, rs1049793 His645Asp. In addition the ABP1 polymorphisms rs45558339 Ile479Met and rs35070995 His659Asn are relevant to Asian and African subjects, respectively. For HNMT the only nonsynonymous polymorphism present with a relevant frequency is rs1801105 Thr105Ile. For HRH1 the polymorphism rs7651620 Glu270Gly is relevant to African subjects only. The HRH2 rs2067474 polymorphism, located in an enhancer element of the gene promoter, is common in all populations. No common nonsynonymous SNPs were observed in the HRH3 gene and two SNPs were observed with a significant frequency in the HRH4 gene: rs11665084 Ala138Val and rs11662595 His206Arg. This review summarizes relevant polymorphisms, discusses controversial findings on association of histamine-related polymorphisms and allergies and other diseases, and identifies topics requiring further investigation.

This thesis describes new and original experimental results on Cu-dependent amine oxidases (CAOs), which show that these enzymes can be conveniently and specifically detected in situ using a peroxidase-coupled activity staining method with 4-Cl-1-naphtole as hydrogen donor substrate. Even more sensitive in situ detection can be achieved using a chemiluminescence-based coupled peroxidase assay which was applied to show that human placenta CAO activity is confined to maternal vessels. A general purification scheme for CAOs is described, and applied to purification of different CAOs. Peptide maps and immunological crossreactivity studies with monoclonal antibodies raised against the purified enzymes showed that they were closely related. Amino acid sequence data for the bovine serum CAO showed that they form a separate group (E.C. 1.4.3.6) with no homology to other enzymes. A cDNA sequence was obtained on the basis of the amino acid sequence data, and this was found to encode a bovine lung CAO, related to bovine serum CAO. The genes for bovine lung and bovine serum CAO are characterized, and Southern blotting analysis of bovine chromosomal DNA shows the existence of a least one more bovine CAO. The purification of human neutrophil CAO is attempted, but it is described how lactoferrin, a protein with many properties in common with CAOs, and with a low degree of sequence identity can account for many observations on human neutrophil CAO. The products of bovine serum CAO oxidation of polyamines are characterised, and 3-aminopropanal is found to be the principal aminoaldehyde produced. Finally, a polyamine-stimulated binding of human placenta CAO to single-stranded DNA is described, and it is reported that the DNA-bound CAO is enzymically active and that the oxidation of DNA-bound polyamines leads to degradation of DNA. In addition to the experimental results, the properties of polyamines and Cu-dependent amine oxidases are reviewed. The polyamines spermidine and spermine interact specifically with nucleic acids and several other molecules. They are synthesised from putrescine, which is a key regulatory molecule formed from ornithine by ornithine decarboxylase, a highly inducible and regulated enzyme. The polyamines can be converted to putrescine by CAOs or spermidine/spermine acetyltransferase and polyamine oxidase. Putrescine is degraded by CAOs, which are also involved in degradation of histamine, a mediator of inflammatory processes. CAOs catalyse the general reaction: R1CH2NHR2 + O2 + H2O-->R1CHO + R2NH2 + H2O2 and in addition to the catabolism of putrescine and histamine CAOs are involved in regulation of growth and apoptosis by to the generation of aminoaldehydes and hydrogen peroxide which have growth inhibitory properties. Several homologous CAOs have been purified and characterized and they form a family with two subgroups. They are homodimers with a relative molecular weight of 180,000 and contain Cu2+ and a modified tyrosine, topaquinone, in the active site. CAOs are present in most tissues with highest amounts in intestine, kidneys, liver and placenta, but the cellular distributions and functions of CAOs are still poorly described, partly due to the use of many different assays and partly due to a broad substrate specificity of the enzymes. However, polyamines and CAOs seem to form a universal system contributing to regulation of growth, differentiation, and apoptosis.

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Thank you both, Rich and Joopiter76. I can't tell you what it means to get some feedback and some possible avenues to investigate.

Joopiter, you mentioned Dr. Amy is talking about mercury and nickel. These are the two metals I have also suspected to be my problem. I am also incredibly allergic to nickel. Metal Chelation intimidates me. I don't want to move anything around and cause more damage in liberating it and then replanting it somewhere else where it could cause even worse problems than where it may be now. Could you tell me where she is talking about this? Does she have her own forum, or a radio show or something? Thanks.

Senior Member

I just can recommend to by Dr. Amys book and DVD: "Autism: Pathways to Recovery" and you may also have a look at the presentations at her homepage. Nickel is associated with viral impact. And with viral die off Nickel will increase. Also you may sign up to her discussion group where you can find thousans of comments of others an herself. You also find her sugestions to treat the different metals. Maybe you take some niacine and this causes this reaction??

About the second link, a quote from another poster, mmorrison, concerning the site and the appearance of a rash after starting the methylation protocol.

That is Dr Amy Yasko's forum, a very large site but with a lot of helpful information and nice people. Most of the people over there are parents who are treating kids who are on the autism spectrum. I spent a lot of time over there when I was starting in on this protocol.

If you sign up over there and just search on "rash" I'm sure you'll find lots of mentions. The general idea seems to be that when the methylation cycle starts working better, for some reason viruses etc that have been dormant become active again, leading to rashes etc. The body then mounts an immune response and starts attacking the now-active pathogen. So really, this is a good thing, according to this theory. Of course, you need to track your body (or in their case, their child's body) closely, because it's tricky to tell the difference between a good reaction and a bad reaction. You might consider backing off on your supps and/or doses to see whether or not the outbreak clears up?

Senior Member

How long does your rash last? I have occasional rashes which puzzled me until I realised they were niacin flushes. They started when I changed to B right from another B complex.

It starts with a severe burning feeling at the top of my head, then the rash develops, moving down my body. It mainly affects face, neck, back, elbows, and knees. It's bright red, itchy and burning. After about 15 minutes it starts to disappear and within 30 minutes it's gone.

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I think my interpretation of a rash differs from yours. This is not a niacin flush. The erythemic flush associated with niacin. This is a bonified rash, in which does not dissappear for however long it takes the lesions making up the rash to heal on the skin. In fact, from the start up, I still don't have some of the rash cleared.

Lets see if I can explain this occurence. After starting the protocol, I had a day in which I experienced a heavy pins and needles heat sensation through out my body. It started over my thymus and radiated up to my head, my arms, and my trunk. This lasted the entire day. I was diaphoretic. I experienced bumps across the right side of my neck, in which always hurts, and my upper arm on the right as well. Also my upper thighs on both legs, and the crease behind my right knee. The pins and needles feeling was something very similar to which I had also felt during one of my anaphylatic reactions I have had previously. The itch I cannot describe, except to say, relentless, intense, and unable to not scratch. Its that crazy itch, one that would make you plumb crazy if you couldn't reach it, itch. This is what I associate with mass Mast Cell degranulation. And then I had the appearance of lesions with the rash. Actually, the bumps of the rash developed into lesions after scratching. My entire body is not covered. I did not have the erythemia I have had with prior anaphylactic reactions, nor anything else similar to those reactions. I don't think what I experienced was a true allergic reaction at all to my starting this protocol in the true allergy sense, as I would still be reacting this way while continuing with it.

I am still doing the protocol, and doing very well despite this one time rash in which has yet to heal completely. Its just been a little worrisome, but not a deal breaker for me.

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So does any of this sound familar to any of you? Ever heard about it happening to someone else?

I guess my concern is whether this is due to start up, bacterial infection, viral aspect, or a detox reaction.

In a previous post on this thread, I found references to mastocytosis as well, which honestly, I found a little alarming concerning the similarities I have experienced with the symptoms and experiences of those with mastocytosis. Guess I am looking for a little direction to investigate while I proceed on with Freddds protocol and before I incorporate some of Rich's protocol.

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Due to the experience of a rash when I started Freddd's methylation protocol and the conversations that have taken place here, I wanted to post a few things concerning this particular issue for me.

I do have leaky gut and have known this for quite a few years, and have been treating it various ways. Although experiencing quite a bit of positive results in doing so, I have yet to attain a resolution to this. In doing more research I have increasingly become interested in celiac disease and the resulting rash called dermatitis herpatiformis. In bacterial translocation, (the medical term for leaky gut), a folate deficiency and vitamin b deficiency results, the folate deficiency being associated with DH. Vitamin B with multiple skin rashes such as Pellagra, etc.

I found one of the treatments on the non-pharma side is nicotinamide. And I come to our conversations here. For a long time I resisted adding this to my regimen as I feared the so called reaction of itching, flushing, and rash. I feared it because I was already experiencing it without its addition.

At the start of Freddd's protocol, this is exactly what I experienced. (B-Right??) It was only after adding additional nicotinamide, that I have come up with some comparisons. Similar in reaction to the B-Right, nicotinomide gave me a warm, pleasant, fuzzy well being sensation. I have had trouble regulating my body temp for quite a few years. This warm, fuzzy feeling is welcome as it has gotten cold here, and for once, I am not.

With the addtional nicotinamide, I stay warm, but I do not flush, I do not itch, and the warmth stays with me for quite a while. I do not react in the typical 20 minutes after ingestion, but seem to react one to two hours after ingestion. I have not developed any more rash or lesions.

So in addtion to the two B-Right I take per day, I am now taking additional B1, B2, and nicotinamide (B3), and biotin.

I am up to 40 of ad B12, and 30 of MB12, 3200 methylfolate, and also added in 1600 of folinic acid.

My rash/lesions are changing in looks and healing. It used to be when I had an injury, it would take forever to heal and the injury would turn into something abnormal and granulate and keep granulating for months on end. At the very beginning prior to becoming so very ill, I kicked it off with a diffuse rash on my arms, chest, and back just so similar to DH.

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I'm glad to hear that you have found something to help with the rash, and that it seems to be abating.

With regard to leaky gut, from my own experience (I don't have CFS, but I do have occasional gut obstruction as a result of rectal cancer surgery 11 years ago) I believe that leaky gut can produce rashes. When I've had a bowel obstruction, which stretches the upstream part of the intestine and produces some temporary damage to it, after it has cleared I've observed that I usually develop a rash, which then clears in less than a day. I interpret this to be due to a temporary case of leaky gut, which resolves as the gut heals. During the time the gut is leaky, presumably bacteria and/or undigested food matter are able to enter the blood stream, and the immune system mounts a response to them, producing the rash. At least, that's my interpretation, and I have involuntarily repeated this "experiment" several times!